A novel approach to the design of new antimicrobial agents has been developed. The overall purpose of the program is the rational design and synthesis of compounds that have combined anti-bacterial, anti-viral and anti-fungal activity. Specifically targeted in the rational design are enveloped viruses such as herpes viruses and HIV. The new compounds have novel structural features which include a dimeric attachment of a known hydrophobic antimetabolite (for example, aminoadamantane analogues) through a very hydrophilic bridge. The hydrophilic portion of the molecule has a high affinity for glycoprotein components of the microbial cell wall. This affinity will deliver the toxic moieties to the cell surface, providing a mechanism for efficient activity. The potential exists for inhibition of replication of such viruses as HIV and, through the attachment of the toxic molecule to the viral coat, a mechanism for killing the virus. Using this strategy, several compounds were examined and certain of these possessed impressive antimicrobial potency. One potent bis-adamantamine analogue (B.V. Shelty, U. S. Patent No. 5,221,693) has been licensed through the NIH technology transfer program for development as a broad spectrum antimicrobial drug, especially for the treatment of gingival infections. Several additional bis-adamantamine analogues have been synthesized to determine the structure-activity relationship for anti-HIV activity. Several new structural features have been incorporated into the new analogues. For example, compounds have been synthesized that contain a bis-Schiff base functionality incorporated into the hydrophilic bridge. This reactive functionality is designed to react with nucleophiles present on HIV protein. Several analogues are now being tested.